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Title
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Crystal structures of two mutant neuraminidase-antibody complexes with amino acid substitutions in the interface.
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Authors
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W.R.Tulip,
J.N.Varghese,
R.G.Webster,
W.G.Laver,
P.M.Colman.
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Ref.
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J Mol Biol, 1992,
227,
149-159.
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PubMed id
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Abstract
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The site on influenza virus N9 neuraminidase recognized by NC41 monoclonal
antibody comprises 19 amino acid residues that are in direct contact with 17
residues on the antibody. Single sequence changes in some of the neuraminidase
residues in the site markedly reduce antibody binding. However, two mutants have
been found within the site, Ile368 to Arg and Asn329 to Asp selected by
antibodies other than NC41, and these mutants bind NC41 antibody with only
slightly reduced affinity. The three-dimensional structures of the two mutant
N9-NC41 antibody complexes as derived from the wild-type complex are presented.
Both structures show that some amino acid substitutions can be accommodated
within an antigen-antibody interface by local structural rearrangements around
the mutation site. In the Ile368 to Arg mutant complex, the side-chain of Arg368
is shifted by 2.9 A from its position in the uncomplexed mutant and a shift of
1.3 A in the position of the light chain residue HisL55 with respect to the
wild-type complex is also observed. In the other mutant, the side-chain of
Asp329 appears rotated by 150 degrees around C alpha-C beta with respect to the
uncomplexed mutant, so that the carboxylate group is moved to the periphery of
the antigen-antibody interface. The results provide a basis for understanding
some of the potential structural effects of somatic hypermutation on
antigen-antibody binding in those cases where the mutation in the antibody
occurs at antigen-contacting residues, and demonstrate again the importance of
structural context in evaluating the effect of amino acid substitutions on
protein structure and function.
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